Pharmacotherapy of hepatitis. Causes, symptoms and treatment of drug-induced hepatitis

The "basic" therapy for liver damage is to saturate it with glucose (+ potassium preparations, vitamins) for sufficient glycogen formation.

Membrane protectors (although the effectiveness of these drugs is questioned by many) include Essentiale, silymarin (karsil, hepabene, silibor, etc.), cyanidanol.

Essentiale prescribed for fatty hepatosis, cirrhosis of the liver of alcoholic etiology, toxic hepatitis, as well as for psoriasis, toxicosis of pregnancy, kidney disease.

Ademetionine(heptral) is a derivative of methionine. Participates in the synthesis of phospholipids, glutathione (antioxidant) and polyamines (hepatocyte proliferation and liver regeneration). Has antidepressant action.

Chronic viral hepatitis.

For the treatment of chronic viral hepatitis B and hepatitis of mixed etiology with the participation of the hepatitis B virus, α2а and α2 b -interferons and lamivudine (zeffix).

Interferons prevent the replication of the virus in the cell and have an immunomodulatory effect. In addition, they are able to stimulate the phagocytic activity of macrophages and the cytokinetic activity of T cells. They are prescribed under the control of the level of biochemical parameters, anti-HBe-Ag. There is evidence that the effect of interferons is higher when combined with lamivudine, ribaverine. Lamivudine is an analogue of nucleosides. The inclusion of the lamivudine metabolite in the viral DNA chain blocks further formation of viral DNA.

For the treatment of chronic viral hepatitis C and liver cirrhosis of viral etiology, combinations are used α-interferon With ribaverin . ribaverin is an analogue of nucleosides. Able to inhibit viral RNA polymerase.

In the treatment of chronic hepatitis C, incl. forms resistant to treatment with conventional α-interferons are used pegylated interferons (Peg-IFN-IFN, connected to a molecule of monomethoxypolyethylene glycol, so they are more slowly eliminated from the body).

Symptomatic therapy for liver diseases

Ascites. Its development is based on portal hypertension, hypoproteinemia, activation of the RAAS.

Therefore, with ascites, the intake of sodium, liquids is limited and diuretics are prescribed: the use of aldosterone antagonists is most indicated, often in combination with loop diuretics (see section "Circulatory failure")

Skin itching. The origin of itching in cholestasis is associated with the accumulation of bile acids. Therefore, drugs that bind bile acids (cholestyramine, cholestipol, ursodeoxycholic acid) are used; inducers of microsomal enzymes (phenobarbital, rifampicin); effective opioid antagonist naloxone, serotonin receptor antagonist ondansitron.

With the aim of relief and prevention of bleeding from varicose veins of the esophagus with portal hypertension, analogues of somatostatin (octreotide) and vasopressin are used. Introduction through the endoscope of sclerosing agents.

In patients with varicose veins without bleeding, the drugs of choice are non-selective β-blockers which reduce the risk of bleeding by 40%. In case of intolerance to β-blockers, prescribe isosorbide mononitrate.

encephalopathy. Its progression may be reduced restriction of protein intake, appointment lactulose(helps accelerate the transit of nitrogenous compounds through the intestines), antibacterial drugs (neomycin, metronidazole, vancomycin), which reduce the formation of ammonium by bacteria, ornithine, which reduces hypoammonemia by enhancing ammonium metabolism.

The basis of therapy chronic active (autoimmune) hepatitis (CAH) are GCS. Most often prescribed prednisolone or methylprednisolone. Often added to treatment cytostatic - azathioprine while reducing the dose of each drug by half.

- reactive inflammatory liver damage caused by the use of hepatotoxic drugs. Symptoms of drug-induced hepatitis may include nausea, vomiting, loss of appetite, constipation or diarrhea, jaundice, dark urine, and light-colored feces. Diagnosis of drug-induced hepatitis is made on the basis of anamnesis, determination of the level of liver tests, ultrasound of the liver. Treatment of drug-induced hepatitis requires the abolition of the pharmaceutical product that caused liver damage, detoxification therapy, and the appointment of hapatoprotectors.

General information

Drug-induced (drug) hepatitis is damage to liver tissues as a result of toxic damage to hepatocytes by metabolites of medicinal substances, with the development of reactive inflammation and necrosis of liver cells. Drug-induced hepatitis complicates ongoing pharmacotherapy in 1-28% of cases and in 12-25% of cases leads to the development of liver cirrhosis and liver failure. Women suffer from drug-induced hepatitis 2-3 times more often than men. A special section of gastroenterology, hepatology, deals with the study and treatment of drug-induced hepatitis.

The reasons

The most important function of the liver in the body is the neutralization and neutralization of toxic substances entering it with the bloodstream. Metabolism and utilization of chemical and biological toxins occurs under the action of the enzymatic neutralizing system of hepatocytes, followed by the removal of harmful products from the body. The process of utilization of toxic substances takes place in the liver in several stages, during which metabolites are formed - intermediate products of biotransformation. The metabolites of some drugs are even more hepatotoxic than the drugs themselves. Long-term use of such drugs or their high dosage leads to the depletion of detoxifying enzyme systems and damage to hepatocytes, resulting in the development of drug-induced hepatitis.

To date, more than a thousand names of drugs are known that lead to the development of drug-induced hepatitis. The toxicity of the action of drugs increases with the combined use of 2-3 drugs, and with the simultaneous use of 6 or more drugs, the likelihood of toxic liver damage increases to 80%. The rate of development of drug-induced hepatitis against the background of taking medications varies from several days to several years.

Risk factors for the development of drug-induced hepatitis include genetically determined hypersensitivity to any drug; the presence at the time of taking the drug chronic hepatitis, viral hepatitis, autoimmune hepatitis, ascites; alcohol intake or toxic effects of solvents, toxic gases against the background of drug therapy; pregnancy; protein deficiency in the diet; stress; kidney failure, heart failure, etc.

The main groups of drugs that cause drug-induced hepatitis include:

• Tuberculosis drugs (rifampicin, isoniazid)
• Antibiotics: tetracyclines (tetracycline, chlortetracycline, dixycycline), penicillins (benzylpenicillin, amoxicillin, etc.), macrolides (erythromycin)
• Sulfonamides (sulfamethoxazole + trimethoprim, sulfadimethoxine, etc.)
• Hormones (steroid hormones, oral contraceptives, etc.)
• NSAIDs (diclofenac, ibuprofen)
• Anticonvulsants and antiepileptics (phenytoin, carbamazepine, clonazepam, etc.)
• Antifungals (amphotericin B, ketoconazole, fluorocytosine)
• Diuretics (hydrochlorothiazide, furosemide, etc.)
• Cytostatics (methotrexate)
• Preparations for the treatment of arrhythmia, diabetes, peptic ulcer and more. others

The list of drugs that have a hepatotoxic effect is far from being exhausted by the named drugs. Drug-induced hepatitis can be caused by almost any drug, and especially by a combination of several drugs.

Symptoms of drug-induced hepatitis

Drug-induced hepatitis can occur in acute or chronic form. Acute drug-induced hepatitis, in turn, are divided into cholestatic, cytolytic (occurring with necrosis and fatty hepatosis) and mixed.

The symptoms of drug-induced hepatitis are similar to those of other types of hepatitis. Dominant in the clinical picture are dyspeptic disorders: loss of appetite, nausea, belching bitterness, vomiting, diarrhea or constipation, weight loss. The main clinical manifestations may be preceded by a prodromal period with asthenic or allergic syndrome. With drug-induced hepatitis, moderate pain, heaviness, discomfort in the right hypochondrium are disturbing; palpation determines hepatomegaly, liver tenderness. Sometimes, against the background of drug-induced hepatitis, jaundice, pruritus, fever, lightening of feces and darkening of the color of urine develop.

In some cases, drug-induced hepatitis can be detected only on the basis of changes in blood biochemical parameters. Acute drug-induced hepatitis, which proceeds with the formation of submassive necrosis, quickly leads to cirrhosis of the liver. With massive necrosis of the liver, liver failure develops.

Diagnostics

In the process of diagnosing drug-induced hepatitis, it is important to exclude viral hepatitis, cholelithiasis, liver tumors, and pancreatic cancer. When taking anamnesis, it is important to find out the causal relationship of liver damage with the use of hepatotoxic drugs.

If drug-induced hepatitis is suspected, biochemical liver tests are examined, in which the activity of transaminases (AST, ALT) and alkaline phosphatase, the level of bilirubin, and globulin fractions increase. A coagulogram, a general analysis of urine and blood, a coprogram is being studied.

Ultrasound of the abdominal organs reveals a diffuse enlargement of the liver, but does not allow us to judge the cause of hepatitis.

Treatment of drug-induced hepatitis

The first step in treating drug-induced hepatitis is to stop the suspected drug causing liver damage and replace it with a safer alternative. It is strictly forbidden for the patient to change medications on his own. In order to remove toxic metabolites from the body, detoxification infusion therapy, plasmapheresis, and, in severe cases, hemodialysis are performed.

To restore damaged liver cells, hepatoprotective drugs (essential phospholipids, ademethionine, methionine) are prescribed. When prescribing drugs with a known hepatotoxic potential, it is recommended to take preventive hepatoprotectors, which helps prevent the development of drug-induced hepatitis.

Forecast and prevention

In severe cases, with lightning-fast development of drug-induced hepatitis or massive necrosis of the hepatic parenchyma, cirrhosis, liver failure, sometimes hepatic coma and death develop. With the timely cancellation of the hepatotoxic drug in most cases, complete recovery occurs.

Prevention of drug-induced hepatitis consists in the rational use of medications, monitoring side effects, taking drugs only as directed by a doctor, and eliminating additional toxic effects. Against the background of long-term drug therapy, the appointment of hepatoprotectors is recommended. Patients who are forced to take medication for a long time should periodically examine the level of transaminases in order to identify drug-induced hepatitis at an early stage.

The liver is one of the largest and most complex human organs and plays a critical role in almost every bodily function. The liver is the "first line of defense", a key link in the detoxification system, a powerful filter that cleanses the blood of harmful substances and thus protects the entire body. The liver is involved in many pathological processes. Its damage causes serious disturbances in metabolism, immune response, detoxification and antimicrobial protection.

The liver is the largest digestive gland. It produces bile, which, entering the duodenum, promotes the digestion and absorption of fats and fat-soluble vitamins. Violation of the outflow of bile not only adversely affects the processes of digestion, but also adversely affects the state of the nervous system (it is not without reason that an irritable person is called a "bilious person"), causes itching and discoloration of the skin.

The liver is involved in the metabolism of proteins, amino acids, carbohydrates, biologically active substances (hormones, biogenic amines, vitamins), which largely determine the appearance and elasticity of the skin. Its role in immune, protective reactions, including the protection of the skin from external influences of microorganisms, is also important. Suffice it to say that up to 95% of antigenic substances are concentrated in the liver and then neutralized. properties alien to the body, and capable of affecting both internal organs and skin.

The liver consists of structural components - lobules. The number of lobules in the liver reaches 500 thousand. These structural and functional elements have the form of a multifaceted prism 1.5–2 mm high. Each such lobule, consisting of many liver cells - hepatocytes, has its own system of bile ducts, nerve fibers and blood vessels.

The structure of the bloodstream of the liver is unusual. Unlike other organs, there are two supplying blood vessels here: the portal vein, through which 70–80% of the total volume of blood flowing to the liver enters, and the hepatic artery, which delivers the remaining 20–30% of the blood.

The blood flowing to the hepatocytes through these vessels is extremely rich in various nutrients. An insignificant part of them is spent by the liver cells for their energy and building needs, another part is used as a raw material for the production of bile, and the third, having processed and neutralized, is returned to the bloodstream again.

The efferent vessels drain into the central vein located in the middle of the lobule. Gradually enlarging, they form 2-3 hepatic veins, which flow into the inferior vena cava, which carries blood to the right atrium.

Bile, which is synthesized by hepatocytes, flows through a special system of ducts, which begins with bile capillaries located between rows of liver cells. Merging, the capillaries form bile ducts, enlarged and then connected to the common hepatic duct. After leaving the gate of the liver, this duct merges with the cystic duct and forms the common bile duct. Bile enters the duodenum through the common bile duct.

Bile enters directly from the liver into the intestines only during the digestion of food. If the intestines are empty, the bile secreted continuously by the liver travels through the cystic duct to the gallbladder, a pear-shaped reservoir containing approximately 40–60 cm3 of bile. The topography of the liver, gallbladder is shown in Fig. 9.6.

Severe liver damage is viral hepatitis - infectious diseases caused by several types of hepatotropic viruses.

Rice. 9.6.

Viral hepatitis- a group of infectious diseases with a primary lesion of the liver. The disease is characterized by a significant polymorphism of clinical manifestations (from subclinical to severe). In cases of severe course, general intoxication, jaundice, hemorrhages and other signs of liver failure are characteristic.

Etiology. Viral hepatitis can be caused by viruses A, B, C and other types.

The reservoir and the only source of infection is a sick person or a virus carrier.

The mechanism of transmission of viral hepatitis A is fecal-oral. Ways of transmission - alimentary, water, contact-household. The susceptibility to the disease is high.

The mechanism of transmission of viral hepatitis B is parenteral. Transmission of infection occurs during blood transfusion (12–20 cases per thousand blood transfusions), microtrauma. Sexual, transplacental routes of transmission are possible.

The mechanism of transmission of viral hepatitis C is parenteral, characterized by a chronic course.

There is no cross immunity between the different forms.

Pathogenesis. There are phases of introduction of pathogens: enteral (or nasopharyngeal) phase, regional lymphadenitis and binge of viruses into the liver through the lymphatic pathways, primary viremia and hematogenous introduction of pathogens into the liver, phase of parenchymal diffusion, unstable localization in the liver and secondary viremia, persistent localization and release from the pathogen .

Necrosis of hepatocytes causes the release of liver enzymes into the blood.

Violation of the formation and excretion of bile is accompanied by an increase in the content of bilirubin and the appearance of bile acids in the urine, an increase in phosphatase and cholesterol in the blood.

The inflammatory process is characterized by an increase in the level of gamma globulins and a change in protein sedimentary samples.

Violation of liver function leads to the accumulation of aromatic compounds, ammonia, indole, PVC, lactic acid in the blood. Endotoxinemia can lead to encephalopathy, hemorrhagic syndrome.

Changes in protein, enzymatic, electrolyte, hormonal metabolism.

Clinic. The incubation period for type A viral hepatitis is 7-50 (usually 14-30) days, for type B viral hepatitis - 40-180 (usually 60-120) days, for type C viral hepatitis - 14-50 days.

The midlife period in 70% of cases is accompanied by dyspeptic syndrome (poor appetite, nausea, vomiting, abdominal pain), fever up to 38–39 ° C, asthenovegetative, artalgic, catarrhal syndromes and a mixed course are possible. Already at this stage of the development of the disease, the liver increases.

The icteric period is noted for 2-6 weeks, but can range from 1 day to several months. At the same time, body temperature normalizes, urine darkens and feces become discolored. In the blood, there is an increase in the level of ALT and bilirubin, which reflects the severity of the process. With a mild course, the level of bilirubin does not exceed 85 mmol / l, ALT - 10-12 nmol / l. With a course of moderate severity, the level of bilirubin does not exceed 170 mmol / l, ALT - 12 nmol / l and above. In severe cases, the level of bilirubin rises to 170-300 mmol / l, dysproteinemia is noted, precoma and hepatic coma develop.

A severe complication of viral hepatitis can be acute liver failure (ARF).

With a lightning-fast form, bleeding, swelling of the brain and lungs, and the addition of sepsis become formidable signs of impending death.

In 5-12% of cases, chronic hepatitis is formed, often occurring with poor symptoms (dyspepsia, moderate hepatomegaly, recurrent mild jaundice). A severe, active variant of the course of chronic viral hepatitis is also possible.

Treatment. Bed rest is extremely important in the acute period.

The diet eliminates indigestible fats. Liquid - in the amount of 2-3 liters per day. Alkaline mineral waters eliminate dyspepsia.

With a mild course of hepatitis against the background of a diet and an appropriate regimen, multivitamin preparations, potassium orotate, methyluracil, and the essential amino acid methionine are indicated.

In the course of hepatitis of moderate severity against the background of a diet and an appropriate regimen, intravenous drip administration of a 5% glucose solution, a 5–10% albumin solution, hemodez, rheopolyglucin and other infusion solutions, cytochrome C is indicated. In hepatitis B, patients with high levels ALT and HBV DNA, as well as with histological signs of necrosis and inflammation in the liver, interferon preparations (primarily pegylated) and nucleoside analogues (lamivudine (Epivir®), entecavir (Baraclud)) are prescribed. Pegylated interferons have a number of advantages over standard interferons - improved pharmacokinetic parameters, higher antiviral activity, low antigenicity, ease of use. When polyethylene glycol (PEG) is conjugated with interferon a-2a, peginterferon a-2a (Pegasys®) is formed. Interferon a-2a is produced by a biosynthetic method using recombinant DNA technology and is a derivative product of a cloned human leukocyte interferon gene introduced and expressed in cells E. coli.

There are six genotypes of the hepatitis C virus that may respond differently to treatment. Before starting treatment for hepatitis, a thorough screening should be carried out to determine the most appropriate approach for the patient. The basis of the treatment of hepatitis C is a combination antiviral therapy based on interferon and ribavirin. Interferon is not always well tolerated, not all genotypes respond equally well to it, and many people receiving it do not complete treatment. Telaprevir (Insivo), boceprevir (Victrelis®) are new antiviral drugs for the treatment of hepatitis C.

In the convalescence phase, hepatoprotectors are used.

In severe hepatitis prescribe glucocorticoids 40-90 mg of prednisolone per day.

In chronic active hepatitis, prednisolone 15–20 mg is used in combination with azathioprine 50–150 mg per day.

Prevention of acute viral hepatitis includes a number of activities, including vaccination. There is no vaccine for hepatitis C. The risk of infection can be reduced by avoiding activities such as:

• giving unnecessary and unsafe injections;
• transfusion of unsafe blood products;
• collection and disposal of unsafe pointed objects and splinters;
• illicit drug use and sharing of injecting equipment;
• unprotected sex with persons infected with hepatitis C;
• sharing sharp-pointed personal items that may be contaminated with infected blood;
• performing tattoos, piercings and acupuncture with contaminated equipment.

Non-infectious hepatitis (non-infectious jaundice) is an inflammatory disease of the liver caused by various causes, including:

• toxic substances (alcohol, drugs, poisons);
• autoimmune aggression on the own cells of the liver and the epithelium of the bile ducts in certain diseases;
• metabolic disorders of copper and iron.

At the first signs of hepatitis: pain in the right hypochondrium, heaviness or discomfort in the abdomen (on the right, where the liver is located), yellowness of the sclera of the eyes and skin, weakness and fatigue, loss of appetite, nausea, dark urine, discoloration of the feces (becomes light) - it is important to see a doctor immediately.

To make a correct diagnosis, the doctor after the examination directs the patient to additional studies:

• blood chemistry;
• blood test for markers of viral hepatitis;
• Ultrasound of the liver and other abdominal organs;
• gastroscopy (EGDS) - to assess the condition of the veins of the esophagus and determine the risk of bleeding;
• liver scintigraphy - a radioisotope study that allows you to evaluate the work of various parts of the organ;
• computed tomography - to assess changes in the liver and other abdominal organs;
• in some cases, a liver biopsy.

The diet for liver damage and the prevention of its changes is based on the exclusion of fatty, fried foods, alcohol, the restriction of salt and protein, and the rejection of alcohol.

Phytotherapy of hepatitis slows down inflammatory and degenerative processes in liver tissues. Plant-based products reduce the likelihood of complications, speed up recovery, reduce jaundice, malaise, pain in the right hypochondrium, rash accompanied by itching.

Peppermint has a calming, antispasmodic, antiseptic, analgesic and choleretic effect, enhances the secretion of the digestive glands, increases bile secretion, promotes the regeneration of liver cells.

Fennel increases the secretion of the digestive glands, has a choleretic, antispasmodic and diuretic effect and some antibacterial effect, increases the secretion of pancreatic juice and bile secretion.

Calendula has an anti-inflammatory effect and at the same time enhances secretory activity, increases bile formation and bile secretion, and also activates regeneration processes.

Most often, liver damage is realized through chemical and immunological mechanisms. Chemical damage to the liver can be caused by natural substances and xenobiotics (drugs). Chemical damage can lead to apoptosis or even necrosis of liver cells. Apoptosis or "programmed cell death" is a physiological process of cell renewal. Apoptosis is found in the process of various liver damage. Unlike necrosis, it develops in individual cells.

To improve liver function, drugs that have a selective effect on the liver are used - hepatoprotectors. Their action is aimed at restoring the liver, increasing the organ's resistance to the action of pathogenic factors, and normalizing its main functions. The algorithm for choosing hepatoprotectors is shown in fig. 9.7.

Rice. 9.7.

Hepatoprotectors based on milk thistle. Medicinal plant milk thistle Silybum marianum) is an effective heaton protector. Milk thistle has been traditionally used in Europe for many centuries and still holds a leading position in liver protection.

Name Silybum derived from the ancient Greek word silly bon is a crest denoting a thistle whose leaves are marked with white spots. An ancient legend says that these white spots are drops of milk that fell from Mary's chest when she was feeding the Christ child during her flight to Egypt. In the Middle Ages, the plant was grown in monasteries and used for medicinal purposes: the roots and leaves were recommended against tumors and erysipelas, as well as for the treatment of the liver. Hepatoprotectors based on milk thistle are necessary for the treatment of liver diseases and for the prevention of various diseases resulting from exposure to adverse environmental factors. By improving the function of the liver, these drugs thus have a positive effect on the condition of the skin.

The main component of milk thistle is silymarin (silibinin).

Silibinin blocks the binding sites of a number of toxic substances and their transport systems due to the phenolic structure.

The metabolic action of silibinin is to stimulate the synthesis of proteins (proteins) and accelerate the regeneration of damaged liver cells (hepatocytes).

Silymarin derivatives exhibit immunomodulatory activity in patients with alcoholic liver cirrhosis.

Milk thistle fruit extract (Karsil® and Letalon® 140) is used for acute and chronic hepatitis, liver cirrhosis, and toxic-metabolic liver damage. The preparations give an antioxidant effect and suppress the peroxide oxidation of polyunsaturated fatty acids in the composition of phospholipid membranes, enhance reparative processes. Silibinin contributes to a significant increase in the content of reduced glutathione in the liver, thereby increasing the protection of the organ from oxidative stress and maintaining its normal detoxification function.

Hepatoprotectors based on other plants. Other plants that protect the liver are medicinal fumes, sandy immortelle, dioica nettle. Large plantain, prickly artichoke, common yarrow, common chicory have a hepatoprotective effect.

Gepabene (fume extract, dry extract of milk thistle fruit) has a choleretic, antispasmodic, hepatoprotective effect. It normalizes the amount of secreted bile, relaxes the smooth muscles of the bile ducts and gallbladder, has antioxidant, membrane-stabilizing activity, stimulates protein synthesis, promotes the regeneration of hepatocytes. It is also used as part of the complex therapy of chronic hepatitis, chronic toxic liver damage.

It is important to remember that the drug is not used for hypersensitivity, acute inflammatory diseases of the liver and biliary tract.

Possible side effects: laxative effect, increased diuresis, allergic reactions. During treatment, you should follow a diet, refrain from drinking alcohol.

Artichoke leaf extract (Hofitol) is a hepatoprotector of plant origin with a choleretic, diuretic and hypoazotemic effect.

It affects the functional activity of liver cells, stimulates the production of enzymes, regulates fat metabolism, increases the antitoxic function of the liver.

The widespread use of hofitol in various fields of medicine is due to:

• effective and multifaceted effect on the organs and tissues of the human body:
• no side effects;
• the ability to use the drug without age restrictions during pregnancy.

Hofitol is included in the standards for the diagnosis and treatment of patients with diseases of the digestive system, as well as in the assortment list of medicines and medical devices that are mandatory for pharmacies "List of vital and essential medicines". The drug has pronounced detoxification properties, normalizes lipid, protein, nitrogen and carbohydrate metabolism, has a therapeutic effect on the liver and kidneys.

Prickly caper extract + western cassia extract + black nightshade fruit extract + tamarix dioecious fruit extract + chebula terminalia fruit extract (Liv.52® K) is a complex preparation containing plants growing in India.

Liv.52® protects the liver parenchyma from toxic agents. Enhances intracellular metabolism and stimulates regeneration. Acts as a therapeutic or prophylactic agent.

Used to improve liver function in infectious and toxic hepatitis, chronic hepatitis and other liver diseases. The drug also increases appetite, improves digestion, promotes the release of gases from the intestines.

When applied, dyspeptic phenomena are possible.

Pumpkin seed oil (Tykveol®) has membrane-stabilizing properties. In addition, the drug reduces inflammation, slows down the development of connective tissue and accelerates the regeneration of the damaged liver parenchyma.

Tykveol has a choleretic effect, normalizes the chemical composition of bile, reduces the risk of developing cholelithiasis and favorably affects its course.

Tykveol is used for chronic liver diseases of various etiologies: chronic liver damage (hepatitis, cirrhosis), cholecystocholangitis and biliary dyskinesia, in the postoperative period of cholecystectomy, for the prevention of gallstone disease.

They also have hepatoprotective effects components of cell membranes of hepatocytes, extracted from the liver of cattle or pigs. Hepatosan is the only preparation of lyophilized hepatocytes from pig liver in the Russian Federation.

In all liver diseases, damage to the membranes of hepatocytes is noted. The cross section of the plasma membrane is shown in Fig. 9.8. Pathogenetically justified is the appointment of therapy that has a regenerating effect on the structure and functions of cell membranes and provides inhibition of the process of cell destruction. Means of this direction of action are preparations containing essential phospholipids (EFL).

The EPL substance is a highly purified soybean extract and contains predominantly phosphatidylcholine (PC) molecules with a high concentration of polyunsaturated fatty acids. The main active ingredient of EPL is 1,2-dilinoleoyl - phosphagidylcholine, the synthesis of which is impossible for the human body.

Membrane stabilizing and hepatoprotective effect of EPL is achieved by direct incorporation of EPL molecules into the phospholipid structure of damaged liver cells, replacement of defects and restoration of the barrier function of the lipid biolayer of membranes. Exogenous EPLs contribute to the activation of transport proteins, which, in turn, has a supporting effect on metabolic processes in liver cells, increases its detoxification and excretory potential.

The hepatoprotective effect of EPL is based on the inhibition of lipid peroxidation (LPO) processes, which are considered as one of the leading pathogenetic mechanisms for the development of liver lesions.

Phospholipids (Essentiale® forte N) contain only highly purified EFL substance.

In clinical practice, it is used in three main areas:

• with liver diseases and its toxic lesions;
• with pathology of internal organs, complicated by liver damage;
• as a method of "drug cover" when using drugs that cause liver damage (tetracycline, rifampicin, paracetamol, indomethacin, etc.).

Essentiale is prescribed for chronic hepatitis, cirrhosis of the liver, fatty degeneration, hepatic coma. It is also used for radiation syndrome and toxicosis of pregnant women, for the prevention of recurrence of cholelithiasis, for preoperative preparation and postoperative treatment of patients, especially in cases of surgical interventions on the liver and biliary tract. At the same time, the use of Essentiale in active hepatitis requires caution, since in some cases it can increase cholestasis and inflammatory activity.

Contraindications: individual intolerance.

Side effects: Very rarely, gastrointestinal upset may occur.

Multivitamin + phospholipids (Essliver® forte): contains essential phospholipids. The composition of the drug includes therapeutic doses of vitamins (B1, B2, B6, B12, tocopherol and nicotinamide).

The action of the drug is aimed at restoring hemostasis in the liver, increasing the resistance of the organ to the action of pathogenic factors, normalizing the functional activity of the liver, and stimulating reparative and regenerative processes.

The drug is used for acute and chronic hepatitis, cirrhosis of the liver, alcohol, drug intoxication, radiation syndrome, psoriasis.

Side effect: rarely - a feeling of discomfort in the abdomen.

Contraindications: hypersensitivity to the drug.

The peculiarity of the drug is the content of essential phospholipids of natural origin, which are easily absorbed by the body.

Domestic drug glycyrrhizic acid + phospholipids (Phosphogliv®) - consists of phosphatidylcholine and trisodium salt of glycyrrhizic acid. Due to the EFL, which is part of the preparation, the severity of inflammatory reactions, necrosis of liver cells, and their fatty infiltration decrease. Glycyrrhizic acid has an immunostimulatory effect, stimulating phagocytosis and the induction of γ-interferon. In addition, it has an antiviral effect, blocking the penetration of viruses into cells, and exhibits antioxidant properties. It is used for acute hepatitis, for the relief of alcohol withdrawal syndrome, in the pre- and postoperative period of cholecystectomy.

The manufacturing technology of the drug is based on know-how, which makes it possible to achieve the formation of nanoballoons (micelles) from phospholipid molecules. For this, homogenization modes under pressure of more than 1000 atm are used.

The drug is made in two forms - for intravenous injection and in the form of capsules for oral administration.

Hepatoprotector Phosphogliv was awarded the State Prize of the Russian Federation in 2003.

Ademetionine (Gsptral®) - has a spatoprotective, antidepressant, detoxication, regenerating, antioxidant, neuroprotective effect.

Replenishes the deficiency of methionine and stimulates its production in the body.

Indications: intrahepatic cholestasis, toxic liver damage, including alcoholic, viral, drug, encephalopathy, depressive and withdrawal symptoms.

Contraindications: hypersensitivity, pregnancy (I and II trimesters).

Side effects: when taken orally - heartburn, pain or discomfort in the epigastric region, dyspepsia, allergic reactions.

Ursodeoxycholic acid (Ursosan®) has a membrane-stabilizing effect, promotes the dissolution of cholesterol stones.

Indications: cholesterol gallstones in the gallbladder; chronic and acute hepatitis. The drug is effective in toxic (including alcoholic, medicinal) liver damage; biliary dyskinesia.

Side effects: diarrhea, calcification of gallstones, allergic reactions.

Contraindications: acute inflammatory diseases of the gallbladder and biliary tract.

The drug should be used to dissolve gallstones only in the presence of cholesterol (X-ray negative) stones no larger than 15–20 mm in size, with preserved patency of the cystic and common bile duct.

Nonsteroidal anabolics dioxomethyltetrahydropyrimidine (Methyluracil), orotic acid (potassium orotate), sodium nucleinate, inosine (Riboxin) - continue to be used in various liver pathologies due to low toxicity and low cost.

Riboxin is a purine derivative. The drug is used for acute and chronic hepatitis, cirrhosis of the liver.

Potassium orotate is a single biochemical precursor of all pyrimidine bases of nucleic acids. It has the greatest effect on the protein-synthetic function, while the duration of the "icteric" period is reduced. The detoxifying effect of the drug is often insufficient. Assign for acute viral hepatitis.

Methyluracil is an analogue of pyrimidine nucleotides, but is practically not included in the exchange as a precursor in the synthesis of nucleotides; accelerates the recovery of the protein-synthetic function of the liver, reduces the symptoms of intoxication and dyspepsia.

Sodium nucleinate - activates protein synthesis. It is mainly used for acute hepatitis. The drug has low toxicity and very rarely causes side effects.

In recent years, the incidence of drug-induced liver injury has increased. Among all drug-induced hepatitis, a large percentage falls on hepatitis caused by antibiotics (tetracycline, erythromycin, oleandomycin, etc.). The mechanisms of liver damage are diverse, which leads to various clinical forms of drug-induced lesions:

• isolated increase in transaminase levels;
• acute (virus-like) hepatitis with jaundice;
• chronic persistent hepatitis;
• chronic active hepatitis;
• cholestatic hepatitis;
• granulomatous hepatitis;
• vascular and tumor lesions of the liver, etc.

Clinical manifestations of liver damage drugs are nonspecific. The data of an objective examination are diverse and are possible in chronic hepatitis of any other genesis.

Medications can induce the activity of monooxygenases in the reactions of hydroxylation of aliphatic and aromatic compounds (barbiturates, meprobamate, ethanol, rifampicin, griseofulvin, hypoglycemic drugs), others can inhibit. Cytochrome P450-dependent monooxygenases are a multienzymatic electron transport system. All cytochromes P450 are heme-containing proteins. Heme iron is usually in an oxidized state (Fe3+). Recovering to the Fe2+ state, cytochrome P450 is able to bind ligands such as oxygen or carbon monoxide. The stages of substrate hydroxylation by cytochrome P450 are shown in Fig. 9.9. The complex of reduced cytochrome P450 with CO has an absorption maximum at 450 nm, which was the basis for the name of these enzymes. There are many cytochrome P450 isoforms involved in the oxidative and reductive metabolism of steroids, fatty acids, retinoids, bile acids, biogenic amines, leukotrienes, and exogenous compounds, including drugs, environmental pollutants, and chemical carcinogens.

Rice. 9.9.

A number of cytochromes P450 are activated with the participation of specific receptors. Only for P450 1A1 and, accordingly, the Ah receptor, a detailed mechanism of action is known. For the remaining P450s, as a rule, a specific receptor has been identified, but the mechanism of action has not yet been described in detail.

Inhibitors of microsomal oxidation bind to the protein part of the cytochrome or to the heme iron - for example, spironolactone, erythromycin. Cimstidip slows down the elimination of diazepam and other benzodiazepines, increasing sedation and increasing toxicity. Microsomal oxidation can be assessed by drug pharmacokinetics and metabolic markers.

Aminazine, sulfonamides, indomethacin, mercazolil, isafenine, etc. cause hepatic necrosis.

Laboratory indicators in some patients are characterized by an increase in the activity of transaminases and a slight increase in the activity of cholestasis enzymes. In another part of the patients, the “cholestatic type” of liver lesions comes to the fore, resembling that of primary biliary cirrhosis. With this type of lesion, there are changes in the activity of enzymes characteristic of patients with intrahepatic cholestasis. Drugs that cause drug cholestasis are presented in table. 9.5.

Table 9.5

drug cholestasis

The development of cholecystitis contributes to the stagnation of bile in the gallbladder. Violation of the normal outflow of bile may be associated with dyskinesia caused by physical inactivity; alimentary factors (irregular meals with long intervals, plentiful meals at night with a preference for meat, spicy, fatty foods, an excess of flour and sweet foods, etc.), emotional overstrain, cholelithiasis and other factors.

Pathogenesis. Pathogens enter the gallbladder by enterogenic (from the intestine), hematogenous (with blood flow), lymphogenous (through lymphatic vessels) pathways.

Depending on the nature of the inflammation, acute catarrhal, phlegmonous and gangrenous cholecystitis are distinguished. Chronic cholecystitis is characterized by a long course with periodic exacerbations. The exacerbation phase is characterized by an increase in the chronic inflammatory process of the gallbladder mucosa, which leads to an increase in body temperature and other signs of the inflammatory process.

Clinic. In the clinic of acute cholecystitis, pain syndrome with signs of inflammation and irritation of the peritoneum predominates.

For the clinical picture of chronic cholecystitis in the acute phase, pain is typical (occurs in the right hypochondrium, spreads to the right shoulder blade, collarbone, shoulder). The occurrence of pain and its intensification is usually associated with a violation of the diet - an abundant intake of fatty, spicy, fried foods, alcoholic beverages, etc. The intensity of the pain increases during the period of exacerbation, periodic pain persists and during the period of remission in the form of minor, nagging pain. Pain may increase with a change in body position, movement. Palpation determines pain in the right hypochondrium, positive pain symptoms of cholecystitis.

Patients complain of belching bitterness, bitter and metallic taste in the mouth, nausea, bloating, stool disorder; vomiting of bitterness is possible.

Body temperature rises in the exacerbation phase. In the blood test in the acute phase, an increase in ESR, neutrophilic leukocytosis, a shift of the leukocyte formula to the left, and eosinophilia are determined.

Mandatory laboratory tests: single cholesterol, amylase, blood sugar, blood group and Rh -factor, coprogram, bacteriological, cytological and biochemical study of duodenal contents. Twice: complete blood count, complete urinalysis, bilirubin and its fractions, AST, AlAT, alkaline phosphatase, GGGP, total protein and protein fractions, C-reactive protein. Mandatory instrumental studies: one-time ultrasound of the liver, gallbladder, pancreas, duodenal sounding (ECHD or other options), esophagogastroduodenoscopy, chest x-ray.

Treatment. In acute acalculous cholecystitis and exacerbation of chronic bacterial cholecystitis, hunger and drinking (hot tea, warm mineral waters) are shown in the first 2-3 days. Then appoint sparing fractional (5-6 times a day) food. The diet should be complete in terms of calories with a normal protein content, some restriction of fats, primarily refractory ones, and a high content of carbohydrates.

Drug therapy(options for antibacterial treatment using one of them).

• 1. Ciprofloxacin inside 500-750 mg 2 times a day for 10 days.
• 2. Doxycycline inside or intravenously drip. On the 1st day, 200 mg per day is prescribed, on the following days, 100–200 mg per day, depending on the severity of the disease.

Duration of taking the drug - up to 2 weeks.

• 3. Co-trimoxazole [sulfamethoxazole + trimethoprim] (Bactrim®, Biseptol®) 480-960 mg 2 times a day with an interval of 12 hours. The course of treatment is 10 days.
• 4. Cephalosporins for oral administration, for example, cefuroxime (Zinnat®) 250-500 mg 2 times a day after meals. The course of treatment is 10-14 days.

Symptomatic drug therapy(used according to indications).

• 1. Domperidone 10 mg 3-4 times a day or trimebutine (Trimedat®) 100-200 mg 3-4 times a day or Meteospasmil 1 cap. 3 times a day. The duration of the course is at least 2 weeks.
• 2. Artichoke leaf extract (Hofitol) 2-3 tab. 3 times a day before meals or allochol 2 tablets. 3-4 times a day after meals or other drugs that increase choleresis and cholekinesis.

The duration of the course is at least 3-4 weeks.

In chronic cholecystitis, choleretic agents are used until the factors that caused stagnation in the gallbladder are eliminated. If the causes of violation of the outflow of bile are unremovable (for example, prolapse of internal organs, inflection of the gallbladder), cholagogues should be taken continuously for a long time. The choice of drug depends on the concomitant biliary dyskinesia and the severity of the process. In an acute inflammatory process and an exacerbation of a chronic one, myotronic antispasmodics and anticholinergics (cholespasmolytics) become the only possible means. These drugs are also the drugs of choice for hypermotor dyskinesia, which is characteristic of young people who eat erratically and lead a stressor lifestyle. Such patients are not contraindicated and choleretics. With hyiomotor dyskinesia (fat, elderly, gynodynamic patients), without exacerbation of chronic cholecystitis, it is possible to use choleretics and very cautious use of cholekinetics only if cholelithiasis (GSD) is excluded.

Choleretics – drugs that stimulate the formation of bile. True choleretics (cholesecretics) increase the secretion of bile due to an increase in its formation.

Preparations containing bile acids or native bile.

Ursosoxycholic acid (Ursosan®) has a high cholesecreting activity and also increases the cholate/cholesterol ratio. When used, stool disorders are possible, more often diarrhea, an increase in the content of transaminases in the blood serum. Contraindicated in exacerbation of cholecystitis, cholangitis, acute and chronic hepatitis, as well as obstruction of the bile ducts, exacerbation of peptic ulcer of the stomach and duodenum, acute intestinal diseases, severe dysfunction of the nights, pregnancy.

Cholenzym: contains bile + pancreas powder + small intestine mucosa powder.

Herbal preparations.

Calamus rhizomes + peppermint leaves + chamomile flowers + + licorice roots + garden dill fruits are part of Fitogastrol (gastrointestinal collection).

Immortelle preparations - immortelle sandy flowers, immortelle sandy flowers sum of flavonoids (Flamin), immortelle sandy flowers + common yarrow herb + peppermint leaves + coriander fruits (choleretic collection No. 2).

Vegetable choleretics - highlander bird grass, centaury grass, coriander fruits, corn columns with stigmas, burdock roots, rowan fruits.

Tansy preparations – tansy flowers (tansy flowers), tansy flowers extract (Tanacehol®), birch leaf extract + St. John's wort herb extract + milk thistle fruit extract + tansy flowers extract (Sibektan®), marigold flowers + peppermint leaves + common tansy flowers + chamomile flowers + common yarrow grass (choleretic collection No. 3)).

Preparations of wormwood - wormwood wormwood, belladonna tincture + + valerian officinalis rhizomes with roots tincture + wormwood tincture (valerian tincture 10 ml, wormwood tincture 8 ml, belladonna tincture 2 ml).

Urolesan and urocholesan contain oregano herb extract + castor bean seed oil + wild carrot seed extract + peppermint leaf oil + fir oil + hop seed oil.

The combined phytopreparation cholagol contains turmeric flavonoids, frangulomodin, mint essential oil, eucalyptus essential oil, sodium salicylate, olive oil.

The choleretic effect is also shown by the fruits of the common barberry, the buds and leaves of birch, the grass of the long-leaved volodushka.

The mechanism of action of herbal preparations is, in particular, the direct stimulation of the secretory function of hepatocytes. This is how the essential oils of juniper (juniper fruit), coriander, oregano, cumin (caraway fruit) act. The magnesium ions that are part of herbal medicines can stimulate the secretion of cholecystokinin by duodenal epithelial cells, which is probably the reason for the cholekinetic effect of arnica, birch, immortelle, wild rose (rose hip fruit, rose hip syrup, rose hip fruit, low vitamin, rose hip seed oil), fennel. A reflex increase in the release of cholecystokinin causes bitterness. These are preparations of dandelion (dandelion officinalis roots), yarrow (common yarrow herb).

When combined with plants with different mechanisms of cholekinetic action, the effect is enhanced. In addition to choleretic activity, many plants have antimicrobial, anti-inflammatory and antihypoxic effects, some have hepatoprotective properties.

Hydrocholeretics - drugs that increase the volume of bile by increasing its water component (bile dilution). This is how drinking mineral water works (balneotherapy).

Cholekinetics - drugs that increase the tone of the gallbladder and relax the bile ducts and the sphincter of Oddi. These include magnesium sulfate, xylitol, sorbitol, extracts from the calamus rhizome, sandy immortelle flowers, lingonberry leaves, cornflower flowers, three-leaf watch leaves, and highlander bird's grass. Cholekinetics are also: herb oregano, shepherd's purse, flowers of marigold officinalis, chamomile (liquid extract of chamomile), fruits of coriander, common juniper, dandelion roots, Tangut rhubarb. Cholekinetic properties are exhibited by creeping thyme herb (thyme grass, liquid thyme extract), common cumin fruits, common fennel, wild rose, common yarrow herb.

The cholekinetic effect is most pronounced in magnesium sulfate, which causes an increase in the secretion of cholecystokinin when taken orally. As a result, the tone of the smooth muscles of the gallbladder increases, the bile ducts and the sphincter of Oddi relax, and bile is released into the duodenum. Xylitol, sorbitol, mannitol have a similar mechanism of action. These drugs also have a laxative effect. It is impossible to prescribe cholekinetics during exacerbation of cholecystitis and in the presence of stones in the gallbladder. The use of cholekinetics is optimal for the so-called blind (or probeless) dubazh (contraindicated in cholelithiasis). The patient drinks on an empty stomach, lying on his side, for 30 minutes in small sips of 100 ml of a 10% (if there is no effect - up to 25%) warm solution of magnesium sulfate, then lies in this position for 1.5–2 hours with a heating pad on the liver area. During the procedure, signs of dyspepsia, discomfort or pain in the right hypochondrium may appear. If, after dubazh, the intestines do not empty, it is necessary to make a cleansing enema. As a treatment procedure, dubazh is done 1 time in 5-7 days, for the prevention of exacerbations of cholecystitis - 1 time in 2-4 weeks. Instead of magnesium sulfate, you can use 200 ml of a 1–2% solution of Karlovy Vary salt, 100 ml of a 20% solution of sorbitol or xylitol.

Cholespasmolytics - drugs that relax the smooth muscles of the gallbladder and biliary tract.

Among cholespasmolytics, M-cholinergic blockers are distinguished: atropine, bellalgin (belladonna leaf extract + benzocaine + metamizole sodium + + sodium bicarbonate), besalol (belladonna leaf extract + phenyl salicylate), metacin, platifillin, as well as myotropic antispasmodics of synthetic and vegetable origin (bencilan (halidor ), drotaverine, papaverine) and combined preparations (for example, nikospan).

The algorithm for choosing antispasmodic therapy is shown in Fig. 9.10.

Rice. 9.10.

Antispasmodics of plant origin - extracts from the flowers of mountain arnica, rhizomes and roots of valerian officinalis and elecampane, St.

The distribution of choleretic drugs into groups is conditional, since most of them have a combination of the above effects, especially herbal remedies.

Barberry ordinary ( Berberis vulgaris), fam. barberry ( Berberidaceae ). A tincture is prepared from the leaves, 15-30 drops are taken 2-3 times a day before meals. Effects of the drug: choleretic, antispasmodic, antimicrobial, anti-inflammatory, diuretic, weak antihypoxic. With prolonged use, there is an increase in blood clotting. The drug is contraindicated in pregnancy.

Sandy immortelle ( helichrysum arenarium), fam. Compositae ( composites ). An infusion is prepared from the flowers (1:10), take 1/3 cup 3-4 times a day before meals. The extract is prescribed 1 g 3 times a day before meals. Contains the extract of immortelle sandy drug flamin, it is taken 0.05 g 3 times a day before meals. Immortelle combines choleretic, cholekinetic, anti-inflammatory, hepatoprotective, stimulating the secretion of digestive glands, antispasmodic, normalizing metabolism, moderately pronounced antihypoxic effects. With prolonged use, an increase in blood clotting is possible. Contraindicated in gastritis with increased secretion, carefully used in cholelithiasis.

Small centaury ( centaurium minus), fam. gentian ( Gentia- paseae ) is used as an infusion of herbs (1:10) 1/3 cup 3 times a day before meals. The effect of the drug is choleretic, cholekinetic, analgesic, gpatoprotector, stimulating the secretion of digestive glands, anti-inflammatory, antimicrobial, antihelminthic, immunotropic, antihypoxic. In therapeutic doses, it is well tolerated. In case of overdose, dyspepsia occurs. Contraindications are hypersecretory gastritis, peptic ulcer of the stomach and duodenum, carefully used for cholelithiasis.

Corn ( Zea mays), fam. cereals ( Roaseae ). Use corn silk, apply in the form of infusion (1: 10) 1/3-1/2 cup 3 times a day before meals. Pharmacological effects: choleretic, cholespasmolytic, anti-inflammatory, hepatoprotective, moderate sedative, diuretic, litholytic, normalizing metabolism, hypoglycemic, hemostatic, moderate antihypoxic. Carefully prescribed for cholelithiasis, it is necessary to control blood clotting with long-term administration.

Peppermint ( Mentha piperita), fam. Lamiaceae ( Lamiaceae ). Infusion of herbs (1:10) is prescribed 1/3-1/2 cup 3 times before meals. Pharmacological effects: choleretic, cholespasmolytic, sedative, vasodilating, analgesic, expectorant, moderate bronchodilator and anti-inflammatory, antihypoxic. Rarely, an allergic reaction to menthol occurs; in children with inhalation, bronchospasm is possible. Peppermint preparations are contraindicated in case of intolerance to the components of the essential oil.

Common tansy ( Tanacetum vulgare), fam. aster ( Asteraceae ). Infusion of flowers (1:10–1:30) is taken 1/3 cup 3 times a day before meals. Pharmacological effects: choleretic, cholekinetic, anti-inflammatory, antipyretic, antimicrobial, antihelminthic, pronounced antihypoxic. In case of overdose, nausea, vomiting, diarrhea, convulsions occur. Contraindications are pregnancy, children's age (up to 5 years), hypersecretory gastritis.

Chicory ordinary ( Cichorium intybus), fam. aster ( Asteraceae ). A decoction of the roots (1:10) is taken 1/4-1/3 cup 3-4 times a day before meals. Pharmacological effects: choleretic, cholekinetic, antimicrobial, anti-inflammatory, diuretic, sedative, moderate cardiotonic and antihypoxic. In case of overdose, tachycardia rarely occurs.

Rosehip May ( Rosa majalis), fam. pink ( Rosaceae ). Rosehip fruit extract (Holosas) take 1 teaspoon 3 times a day before meals. A decoction of rose hips (1:10) is taken 1/3-1/2 cup 3 times a day before meals. Pharmacological effects: choleretic, cholekinetic, hepatoprotective, anti-inflammatory, normalizing metabolism.

Spanish artichoke ( Cynara scolymus), fam. Compositae ( composites ). Dry extract of artichoke contains the drug hofitol. The active ingredients are cynarin and caffeic, chlorogenic, caffeinic acids. They ensure the maintenance of the functions of hepatocytes, cause choleretic and diuretic effects.

milk thistle ( Silybum marianum), fam. aster ( Asteraceae ). Fruits, grass contain silybin, dehydrosilybin and other flavolignans, have choleretic and cholespasmolytic effects, milk thistle flavonoids provide hepatoprotective, antioxidant and anabolic effects (stimulate RNA polymerase), block the production of acetaldehyde. Side effects: diarrhea, increased diuresis. Milk thistle preparations (Karsil®, Silibinin®, Legalon®, Silimar®, Silymarin) are contraindicated in acute inflammatory liver diseases, hypersensitivity to drugs, during pregnancy and lactation, they are used only for health reasons.

celandine ( Chelidonium ), fam. poppy ( Papaveraceae ). Celandine alkaloid chelidopine causes analgesic, antispasmodic, choleretic effects.

Pumpkin ( Cucurbita ), fam. pumpkin ( Cucurbitaceae ). Pumpkin seeds (Tykveol® preparation) contain carotenoids, phospholipids, tocopherols, flavonoids, vitamins B, B2, C, PP, F, saturated and unsaturated fatty acids. The active substances have an antiulcer, hepatoprotective, choleretic effect, inhibit the proliferation of prostate cells.

Combined drugs are effective. 11 the patient is selected 3-4 preparation prescriptions, which should be alternated every 1.5-2 months, which ensures long-term remission and prevention of the formation of gallbladder stones. There are also proprietary combinations.

Allohol contains activated charcoal + bile + nettle leaves + garlic bulbs. Used for chronic hepatitis, cholangitis, acalculous cholecystitis, habitual constipation.

Cholagol, 10 ml bottles, contains turmeric root dye, emodin, magnesium salicylate, essential oils, olive oil. The algorithm for choosing choleretic agents is shown in fig. 9.11.

Rice. 9.11.

Digestive enzyme preparations are prescribed to improve digestion processes.

Pancreatin (Festal, Creon, Panzinorm) is taken for 3 weeks before meals, 1-2 doses.

• Biochemistry: a textbook for universities / ed. E. S. Severina. M., 2009.

Hundreds of suppliers bring hepatitis C medicines from India to Russia, but only M-PHARMA will help you buy sofosbuvir and daclatasvir, while professional consultants will answer any of your questions throughout the therapy.

Main symptoms

1. Jaundice. The symptom is common and is due to the fact that bilirubin enters the patient's blood during liver damage. Blood, circulating through the body, carries it through the organs and tissues, staining them yellow.
2. The appearance of pain in the region of the right hypochondrium. It occurs due to an increase in the size of the liver, leading to the appearance of pain, which is dull and prolonged, or is paroxysmal in nature.
3. Deterioration of well-being, accompanied by fever, headaches, dizziness, indigestion, drowsiness and lethargy. All this is a consequence of the action on the body of bilirubin.

Hepatitis acute and chronic

Hepatitis in patients have acute and chronic forms. In an acute form, they appear in the case of viral liver damage, as well as if there has been poisoning with various types of poisons. In acute forms of the course of the disease, the condition of patients deteriorates rapidly, which contributes to the accelerated development of symptoms.

With this form of the disease, favorable prognosis is quite possible. Except for its transformation into a chronic one. In the acute form, the disease is easily diagnosed and easier to treat. Untreated acute hepatitis easily develops into a chronic form. Sometimes with severe poisoning (for example, alcohol), the chronic form occurs on its own. In the chronic form of hepatitis, the process of replacement of liver cells with connective tissue occurs. It is weakly expressed, goes slowly, and therefore sometimes remains undiagnosed until the onset of cirrhosis of the liver. Chronic hepatitis is treated worse, and the prognosis for its cure is less favorable. In the acute course of the disease, the state of health worsens significantly, jaundice develops, intoxication appears, the functional work of the liver decreases, and the content of bilirubin in the blood increases. With timely detection and effective treatment of acute hepatitis, the patient most often recovers. With a duration of the disease for more than six months, hepatitis becomes chronic. The chronic form of the disease leads to serious disorders in the body - the spleen and liver increase, metabolism is disturbed, complications arise in the form of cirrhosis of the liver and oncological formations. If the patient has reduced immunity, the treatment regimen is chosen incorrectly, or there is alcohol dependence, then the transition of hepatitis to a chronic form threatens the patient's life.

Varieties of hepatitis

Hepatitis A

• in the acute form with jaundice, the liver is seriously damaged;
• with subacute without jaundice, we can talk about a milder version of the disease;
• in the subclinical form, you may not even notice symptoms, although the infected person is a source of the virus and is able to infect others.

Hepatitis B

Hepatitis C

Hepatitis D

Hepatitis E

Hepatitis F

Hepatitis G

Diagnostics

How is hepatitis C treated?

1. The cost of medicines to fight the hepatitis virus is high, and not everyone can buy them.
2. Taking certain drugs is accompanied by unpleasant side effects, including fever, nausea, and diarrhea.

Features of HCV genotypes

• 1a, 1b and 1c;
• 2a, 2b, 2c and 2d;
• 3a, 3b, 3c, 3d, 3e and 3f;
• 4a, 4b, 4c, 4d, 4e, 4f, 4h, 4i and 4j;

How are HCV strains spread around the world?

On the territory of the globe, hepatitis C genotypes are distributed heterogeneously, and most often you can find genotypes 1, 2, 3, and in some areas it looks like this:

• in Western Europe and its eastern regions, genotypes 1 and 2 are most common;
• in the USA, subtypes 1a and 1b;
• in northern Africa, genotype 4 is the most common.

• genotype 1b accounts for ~50% of cases;
• for genotype 3a ~20%,
• ~10% of patients are infected with hepatitis 1a;
• genotype 2 hepatitis was found in ~5% of those infected.

• age of patients. The chance of a cure in young people is much higher;
• it is easier for women to recover than for men;
• the degree of liver damage is important - the favorable outcome is higher with less damage to it;
• the magnitude of the viral load - the less viruses in the body at the time of the start of treatment, the more effective the therapy;
• patient's weight: the higher it is, the more complicated the treatment.

Who is at risk for HCV infection?

• patients receiving blood transfusions;
• patients and clients in dental offices and medical facilities where medical instruments are improperly sterilized;
• due to non-sterile instruments, it can be dangerous to visit a nail and beauty salon;
• lovers of piercings and tattoos can also suffer from poorly processed tools,
• high risk of infection in those who use drugs due to repeated use of non-sterile needles;
• the fetus can become infected from a mother infected with hepatitis C;
• during sexual intercourse, the infection can also enter the body of a healthy person.

How is hepatitis C treated?

What is Sofosbuvir?

The effectiveness of this drug in the fight against HCV was so high that now almost no therapy regimen can do without its use. Sofosbuvir is not recommended for use as monotherapy, but with complex use it shows exceptionally good results. Initially, the drug was used in combination with ribavirin and interferon, which allowed in uncomplicated cases to achieve a cure in just 12 weeks. And this despite the fact that therapy with only interferon and ribavirin was half as effective, and its duration sometimes exceeded 40 weeks. After 2013, each subsequent year brought news of the emergence of more and more new drugs that successfully fight the hepatitis C virus:

• daclatasvir appeared in 2014;
• 2015 was the birth year of ledipasvir;
• 2016 pleased with the creation of velpatasvir.

• Harvoni, a combination of sofosbuvir 400 mg and ledipasvir 90 mg;
• Epclusa, which included sofosbuvir 400 mg and velpatasvir 100 mg.

The emergence of generics

Mechanisms of action

1. Sofosbuvir blocks RNA polymerase, thereby inhibiting the replication of the virus.

1. Daclatasvir, ledipasvir and velpatasvir are NS5A inhibitors that interfere with the spread of viruses and their entry into healthy cells.

Generic manufacturers from India

• Hepcvir is manufactured by Cipla Ltd.;
• Hepcinat - Natco Pharma Ltd.;
• Cimivir - Biocon ltd. & Hetero Drugs Ltd.;
• MyHep is a manufacturer of Mylan Pharmaceuticals Private Ltd.;
• SoviHep - Zydus Heptiza Ltd.;
• Sofovir is the manufacturer of Hetero Drugs Ltd.;
• Resof - manufactured by Dr Reddy's Laboratories;
• Virso - Releases Strides Arcolab.

• Natdac from Natco Pharma;
• Dacihep by Zydus Heptiza;
• Daclahep from Hetero Drugs;
• Dactovin by Strides Arcolab;
• Daclawin by Biocon ltd. & Hetero Drugs Ltd.;
• Mydacla by Mylan Pharmaceuticals.

• Ledifos - releases Hetero;
• Hepcinat LP - Natco;
• Myhep LVIR - Mylan;
• Hepcvir L - Cipla Ltd.;
• Cimivir L - Biocon ltd. & Hetero Drugs Ltd.;
• LadyHep - Zydus.

• Velpanat was released by Natco Pharma;
• the release of Velasof was mastered by Hetero Drugs;
• SoviHep V was launched by Zydus Heptiza.

Requirements for generics

1. It is necessary to observe the ratio of the most important pharmaceutical components in the preparation in terms of qualitative as well as quantitative standards.

1. Compliance with the relevant international standards should be adhered to.

1. Mandatory observance of appropriate production conditions is required.

1. The preparations should maintain an appropriate equivalent of the absorption parameters.

Egyptian generics of sofosbuvir

• MPI Viropack, manufactures Marcyrl Pharmaceutical Industries, one of the earliest Egyptian generics;

• Heterosofir is manufactured by Pharmed Healthcare. Is the only licensed generic in Egypt. On the packaging, under the hologram, there is a hidden code that allows you to check the originality of the drug on the manufacturer's website, thereby eliminating its fake;

• Grateziano, manufactured by Pharco Pharmaceuticals;

• Sofolanork, produced by Vimeo;

• Sofocivir manufactured by ZetaPhar.

Hepatitis Generics from Bangladesh

• Soforal is a generic sofosbuvir containing 400 mg of active ingredient. Unlike traditional packs in bottles of 28 pieces, Soforal is produced in the form of blisters of 8 tablets in one plate;
• Daclavir is a generic of daclatasvir, one tablet of the drug contains 60 mg of the active ingredient. It is also released in the form of blisters, but each plate contains 10 tablets;
• Sofosvel is a generic Epclusa containing sofosbuvir 400mg and velpatasvir 100mg. Pangenotypic (universal) drug, effective in the treatment of HCV genotypes 1 ÷ 6. And in this case, there is no usual packaging in vials, the tablets are packed in blisters of 6 pieces in each plate.
• Darvoni is a complex drug that combines sofosbuvir 400 mg and daclatasvir 60 mg. If it is necessary to combine sofosbuvir therapy with daklatasvir, using drugs from other manufacturers, it is necessary to take a tablet of each type. And Beacon combined them into one pill. Packed Darvoni in blisters of 6 tablets in one plate, sent only for export.

Natco Pharma Ltd.

Hetero Drugs Ltd.

Zydus Heptiza

HCV Therapy 2017

• virus genotype;
• the duration of the illness;
• the degree of liver damage;
• presence / absence of cirrhosis, concomitant infection (for example, HIV or other hepatitis), negative experience of previous treatment.

1. Possible treatment regimens proposed by EASL in the case of hepatitis C monoinfection or co-infection with HIV + HCV in patients without cirrhosis and not previously treated:

• for treatment genotypes 1a and 1b can be used:

• in therapy genotype 2 used without ribavirin for 12 weeks:

• during treatment genotype 3 without the use of ribavirin for a period of therapy of 12 weeks, use:

• in therapy genotype 4 you can use without ribavirin for 12 weeks:

1. EASL recommended treatment regimens for hepatitis C monoinfection or co-infection with HIV/HCV in previously untreated patients with compensated cirrhosis:

• for treatment genotypes 1a and 1b can be used:

• in therapy genotype 2 apply:

• during treatment genotype 3 use:

• in therapy genotype 4 apply the same schemes as for genotypes 1a and 1b.

Treatment with modern HCV drugs

• headaches;
• vomiting and dizziness;
• general weakness;
• loss of appetite;
• pain in the joints;
• a change in the biochemical parameters of the blood, expressed in a low level of hemoglobin, a decrease in platelets and lymphocytes.

Contraindications

• individual hypersensitivity of patients to certain ingredients of medicines;

• patients under the age of 18, as there is no accurate data on their effects on the body;

• women who are pregnant and breastfeeding babies;

• women should use reliable methods of contraception to avoid conception during the period of therapy. Moreover, this requirement also applies to women whose partners are also undergoing DAA therapy.

Storage

• order them through Russian online pharmacies and receive the goods in a few hours (or days) depending on the place of delivery. Moreover, in most cases, even an advance payment is not required;
• order them through Indian online stores with home delivery. Here you will need an advance payment in foreign currency, and the waiting time will last from three weeks to a month. Plus, the need to communicate with the seller in English will be added;
• go to India and bring the drug yourself. This will also take time, plus the language barrier, plus the difficulty of verifying the originality of the goods purchased at the pharmacy. To everything else, the problem of self-exportation will be added, requiring a thermal container, a doctor's report and a prescription in English, as well as a copy of the receipt.